1. Field of the Invention
The present invention relates to the treatment of diabetes-related vascular complications. The treatment method includes the step of administering to the patient a therapeutically effective dosage of alpha-lipoic acid.
2. Description of the Related Art
Epidemiological and experimental evidence both indicate that diabetes is a major risk factor for the development of atherosclerosis and hypertension, and these clinical scenarios lead to aortic aneurysm, heart failure, myocardial infarction and stroke. It has been shown that the diabetic vascular system is associated with endothelial dysfunction and this phenomenon is considered to be a causal factor in the development of atherothrombotic disease, and as one of the earliest abnormalities that can be detected clinically in an individual predisposed to atherosclerosis and hypertension. However, the exact molecular mechanisms responsible for these changes in vascular phenotype in diabetes remain unknown. Further, treatment intended to reverse or delay diabetes-induced decline of vascular function has yet to be implemented.
Dysfunction of the endothelium in a number of vascular diseases, including diabetes, hypertension, and atherosclerosis, is associated with reduced bioavailability of the signaling molecule nitric oxide, which has potent vasodilatory, anti-inflammatory and antiatherosclerotic properties. A large quantity of available evidence indicates that impaired endothelium-derived NO bioavailability is due, in part, to excess oxidative stress. Diseased blood vessels produce increased levels of reactive superoxide anion (O2−) and hydrogen peroxide. Superoxide anion reacts with NO, yielding peroxynitrate, which has the potential of inducing protein modification, DNA damage, apoptosis and inflammation.
Oxidative stress in a physiological setting reflects an excessive bioavailability of Reactive Oxygen Species (ROS), which is the net result of an imbalance between production and destruction of ROS, with the latter being influenced by antioxidant defenses, including antioxidant enzyme (e.g., superoxide dismutase, glutathione peroxidase, and catalase) and chemical antioxidants (e.g., α-lipoic acid (LA) and vitamins). Excessive stress has been shown to promote apoptosis and elicits several inflammatory responses in endothelial cells, including the production of proinflammatory responses in endothelial cells, including the production of proinflammatory cytokines and chemokines TNF-α, IL-1β, along with monocyte chemoattractive protein (MCAP-1 or MCP-1), and an increased surface expression of the cellular adhesion molecules, E-selectin, vascular cell adhesion molecule 1 (VCAM-1) and intracellular adhesion molecule (CAM or ICAM-1). A large portion of the above parameters are altered as a function of diabetes.
Alpha-lipoic acid (LA) is an endogenous short-chain fatty acid that occurs naturally in the human diet and is rapidly absorbed and converted intracellularly to dihydrolipoic acid via NAD(P)H-dependent enzymes. In addition to playing an important role as a cofactor for mitochondrial bioenergetic enzymes, LA and dihydrolipoic acid can scavenge ROS, regenerate other natural antioxidants, such as glutathione, vitamin C and vitamin E, chelate metals ions, and stimulate insulin signaling. LA further improves neurovascular and metabolic abnormalities and may further play a role in cardiovascular protection and as an anti-inflammatory agent. Additionally, it has been shown that LA ameliorates diabetes-related deficits in skeletal muscle glucose metabolism, protein oxidation, as well as the activation by insulin of the various steps of the insulin signaling pathway, including the enzymes AKT/PKB and phosphatidyl inositol 3-kinase.
Thus, a method of treating diabetes-related vascular complications solving the aforementioned problems is desired.